@article{WeyrichLenzFickel2018,
  author    = {Weyrich, Alexandra and Lenz, Dorina and Fickel, J{\"o}rns},
  title     = {Environmental Change-Dependent Inherited Epigenetic Response},
  series = {GENES},
  volume    = {10},
  journal   = {GENES},
  number    = {1},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2073-4425},
  doi       = {10.3390/genes10010004},
  pages     = {15},
  year      = {2018},
  abstract  = {Epigenetic modifications are a mechanism conveying environmental information to subsequent generations via parental germ lines. Research on epigenetic responses to environmental changes in wild mammals has been widely neglected, as well as studies that compare responses to changes in different environmental factors. Here, we focused on the transmission of DNA methylation changes to naive male offspring after paternal exposure to either diet (~40\% less protein) or temperature increase (10 °C increased temperature). Because both experiments focused on the liver as the main metabolic and thermoregulation organ, we were able to decipher if epigenetic changes differed in response to different environmental changes. Reduced representation bisulfite sequencing (RRBS) revealed differentially methylated regions (DMRs) in annotated genomic regions in sons sired before (control) and after the fathers' treatments. We detected both a highly specific epigenetic response dependent on the environmental factor that had changed that was reflected in genes involved in specific metabolic pathways, and a more general response to changes in outer stimuli reflected by epigenetic modifications in a small subset of genes shared between both responses. Our results indicated that fathers prepared their offspring for specific environmental changes by paternally inherited epigenetic modifications, suggesting a strong paternal contribution to adaptive processes.},
  language  = {en}
}
@article{WeyrichLenzJescheketal.2016,
  author    = {Weyrich, Alexandra and Lenz, Dorina and Jeschek, Marie and Tzu Hung Chung, and Ruebensam, Kathrin and Goeritz, Frank and Jewgenow, Katarina and Fickel, J{\"o}rns},
  title     = {Paternal intergenerational epigenetic response to heat exposure in male Wild guinea pigs},
  series = {Molecular ecology},
  volume    = {25},
  journal   = {Molecular ecology},
  publisher = {Wiley-Blackwell},
  address   = {Hoboken},
  issn      = {0962-1083},
  doi       = {10.1111/mec.13494},
  pages     = {1729 -- 1740},
  year      = {2016},
  abstract  = {Epigenetic modifications, of which DNA methylation is the best studied one, can convey environmental information through generations via parental germ lines. Past studies have focused on the maternal transmission of epigenetic information to the offspring of isogenic mice and rats in response to external changes, whereas heterogeneous wild mammals as well as paternal epigenetic effects have been widely neglected. In most wild mammal species, males are the dispersing sex and have to cope with differing habitats and thermal changes. As temperature is a major environmental factor we investigated if genetically heterogeneous Wild guinea pig (Cavia aperea) males can adapt epigenetically to an increase in temperature and if that response will be transmitted to the next generation(s). Five adult male guinea pigs (F0) were exposed to an increased ambient temperature for 2 months, i.e. the duration of spermatogenesis. We studied the liver (as the main thermoregulatory organ) of F0 fathers and F1 sons, and testes of F1 sons for paternal transmission of epigenetic modifications across generation(s). Reduced representation bisulphite sequencing revealed shared differentially methylated regions in annotated areas between F0 livers before and after heat treatment, and their sons' livers and testes, which indicated a general response with ecological relevance. Thus, paternal exposure to a temporally limited increased ambient temperature led to an 'immediate' and 'heritable' epigenetic response that may even be transmitted to the F2 generation. In the context of globally rising temperatures epigenetic mechanisms may become increasingly relevant for the survival of species.},
  language  = {en}
}
@article{GuerreroFickelBenhaiemetal.2020,
  author    = {Guerrero, Tania P. and Fickel, J{\"o}rns and Benhaiem, Sarah and Weyrich, Alexandra},
  title     = {Epigenomics and gene regulation in mammalian social systems},
  series = {Current zoology},
  volume    = {66},
  journal   = {Current zoology},
  number    = {3},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {1674-5507},
  doi       = {10.1093/cz/zoaa005},
  pages     = {307 -- 319},
  year      = {2020},
  abstract  = {Social epigenomics is a new field of research that studies how the social environment shapes the epigenome and how in turn the epigenome modulates behavior. We focus on describing known gene-environment interactions (GEIs) and epigenetic mechanisms in different mammalian social systems. To illustrate how epigenetic mechanisms integrate GEls, we highlight examples where epigenetic mechanisms are associated with social behaviors and with their maintenance through neuroendocrine, locomotor, and metabolic responses. We discuss future research trajectories and open questions for the emerging field of social epigenomics in nonmodel and naturally occurring social systems. Finally, we outline the technological advances that aid the study of epigenetic mechanisms in the establishment of GEIs and vice versa.},
  language  = {en}
}
@article{WeyrichBenzKarletal.2016,
  author    = {Weyrich, Alexandra and Benz, Stephanie and Karl, Stephan and Jeschek, Marie and Jewgenow, Katarina and Fickel, J{\"o}rns},
  title     = {Paternal heat exposure causes DNA methylation and gene expression changes of Stat3 in Wild guinea pig sons},
  series = {Ecology and evolution},
  volume    = {6},
  journal   = {Ecology and evolution},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {2045-7758},
  doi       = {10.1002/ece3.1993},
  pages     = {2657 -- 2666},
  year      = {2016},
  abstract  = {Epigenetic mechanisms convey environmental information through generations and can regulate gene expression. Epigenetic studies in wild mammals are rare, but enable understanding adaptation processes as they may occur in nature. In most wild mammal species, males are the dispersing sex and thus often have to cope with differing habitats and thermal changes more rapidly than the often philopatric females. As temperature is a major environmental selection factor, we investigated whether genetically heterogeneous Wild guinea pig (Cavia aperea) males adapt epigenetically to an increase in temperature, whether that response will be transmitted to the next generation(s), and whether it regulates mRNA expression. Five (F0) adult male guinea pigs were exposed to an increased ambient temperature for 2 months, corresponding to the duration of the species' spermatogenesis. To study the effect of heat, we focused on the main thermoregulatory organ, the liver. We analyzed CpG-methylation changes of male offspring (F1) sired before and after the fathers' heat treatment (as has recently been described in Weyrich et al. [Mol. Ecol., 2015]). Transcription analysis was performed for the three genes with the highest number of differentially methylated changes detected: the thermoregulation gene Signal Transducer and Activator of Transcription 3 (Stat3), the proteolytic peptidase gene Cathepsin Z (Ctsz), and Sirtuin 6 (Sirt6) with function in epigenetic regulation. Stat3 gene expression was significantly reduced (P < 0.05), which indicated a close link between CpG-methylation and expression levels for this gene. The two other genes did not show gene expression changes. Our results indicate the presence of a paternal transgenerational epigenetic effect. Quick adaptation to climatic changes may become increasingly relevant for the survival of wildlife species as global temperatures are rising.},
  language  = {en}
}
@article{WeyrichYasarLenzetal.2020,
  author    = {Weyrich, Alexandra and Yasar, Selma and Lenz, Dorina and Fickel, J{\"o}rns},
  title     = {Tissue-specific epigenetic inheritance after paternal heat exposure in male wild guinea pigs},
  series = {Mammalian genome},
  volume    = {31},
  journal   = {Mammalian genome},
  number    = {5-6},
  publisher = {Springer},
  address   = {New York},
  issn      = {0938-8990},
  doi       = {10.1007/s00335-020-09832-6},
  pages     = {157 -- 169},
  year      = {2020},
  abstract  = {External temperature change has been shown to modify epigenetic patterns, such as DNA methylation, which regulates gene expression. DNA methylation is heritable, and as such provides a mechanism to convey environmental information to subsequent generations. Studies on epigenetic response to temperature increase are still scarce in wild mammals, even more so studies that compare tissue-specific epigenetic responses. Here, we aim to address differential epigenetic responses on a gene and gene pathway level in two organs, liver and testis. We chose these organs, because the liver is the main metabolic and thermoregulation organ, and epigenetic modifications in testis are potentially transmitted to the F2 generation. We focused on the transmission of DNA methylation changes to naive male offspring after paternal exposure to an ambient temperature increase of 10 degrees C, and investigated differential methylated regions of sons sired before and after the paternal exposure using Reduced Representation Bisulfite Sequencing. We detected both a highly tissue-specific epigenetic response, reflected in genes involved in organ-specific metabolic pathways, and a more general regulation of single genes epigenetically modified in both organs. We conclude that genomes are context-specifically differentially epigenetically regulated in response to temperature increase. These findings emphasize the epigenetic relevance in cell differentiation, which is essential for the specific function(s) of complex organs, and is represented in a diverse molecular regulation of genes and gene pathways. The results also emphasize the paternal contribution to adaptive processes.},
  language  = {en}
}
@misc{WeyrichYasarLenzetal.2020,
  author    = {Weyrich, Alexandra and Yasar, Selma and Lenz, Dorina and Fickel, J{\"o}rns},
  title     = {Tissue-specific epigenetic inheritance after paternal heat exposure in male wild guinea pigs},
  series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {5-6},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-51652},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-516525},
  pages     = {15},
  year      = {2020},
  abstract  = {External temperature change has been shown to modify epigenetic patterns, such as DNA methylation, which regulates gene expression. DNA methylation is heritable, and as such provides a mechanism to convey environmental information to subsequent generations. Studies on epigenetic response to temperature increase are still scarce in wild mammals, even more so studies that compare tissue-specific epigenetic responses. Here, we aim to address differential epigenetic responses on a gene and gene pathway level in two organs, liver and testis. We chose these organs, because the liver is the main metabolic and thermoregulation organ, and epigenetic modifications in testis are potentially transmitted to the F2 generation. We focused on the transmission of DNA methylation changes to naive male offspring after paternal exposure to an ambient temperature increase of 10 degrees C, and investigated differential methylated regions of sons sired before and after the paternal exposure using Reduced Representation Bisulfite Sequencing. We detected both a highly tissue-specific epigenetic response, reflected in genes involved in organ-specific metabolic pathways, and a more general regulation of single genes epigenetically modified in both organs. We conclude that genomes are context-specifically differentially epigenetically regulated in response to temperature increase. These findings emphasize the epigenetic relevance in cell differentiation, which is essential for the specific function(s) of complex organs, and is represented in a diverse molecular regulation of genes and gene pathways. The results also emphasize the paternal contribution to adaptive processes.},
  language  = {en}
}
@misc{WeyrichJeschekSchrapersetal.2018,
  author    = {Weyrich, Alexandra and Jeschek, Marie and Schrapers, Katharina T. and Lenz, Dorina and Chung, Tzu Hung and Ruebensam, Kathrin and Yasar, Sermin and Schneemann, Markus and Ortmann, Sylvia and Jewgenow, Katarina and Fickel, J{\"o}rns},
  title     = {Diet changes alter paternally inherited epigenetic pattern in male Wild guinea pigs},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {1065},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-46003},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-460031},
  pages     = {14},
  year      = {2018},
  abstract  = {Epigenetic modifications, of which DNA methylation is the most stable, are a mechanism conveying environmental information to subsequent generations via parental germ lines. The paternal contribution to adaptive processes in the offspring might be crucial, but has been widely neglected in comparison to the maternal one. To address the paternal impact on the offspring's adaptability to changes in diet composition, we investigated if low protein diet (LPD) in F0 males caused epigenetic alterations in their subsequently sired sons. We therefore fed F0 male Wild guinea pigs with a diet lowered in protein content (LPD) and investigated DNA methylation in sons sired before and after their father's LPD treatment in both, liver and testis tissues. Our results point to a 'heritable epigenetic response' of the sons to the fathers' dietary change. Because we detected methylation changes also in the testis tissue, they are likely to be transmitted to the F2 generation. Gene-network analyses of differentially methylated genes in liver identified main metabolic pathways indicating a metabolic reprogramming ('metabolic shift'). Epigenetic mechanisms, allowing an immediate and inherited adaptation may thus be important for the survival of species in the context of a persistently changing environment, such as climate change.},
  language  = {en}
}
@article{WeyrichJeschekSchrapersetal.2018,
  author    = {Weyrich, Alexandra and Jeschek, Marie and Schrapers, Katharina T. and Lenz, Dorina and Chung, Tzu Hung and Ruebensam, Kathrin and Yasar, Sermin and Schneemann, Markus and Ortmann, Sylvia and Jewgenow, Katarina and Fickel, J{\"o}rns},
  title     = {Diet changes alter paternally inherited epigenetic pattern in male Wild guinea pigs},
  series = {Environmental Epigenetics},
  volume    = {4},
  journal   = {Environmental Epigenetics},
  number    = {2},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {2058-5888},
  doi       = {10.1093/eep/dvy011},
  pages     = {12},
  year      = {2018},
  abstract  = {Epigenetic modifications, of which DNA methylation is the most stable, are a mechanism conveying environmental information to subsequent generations via parental germ lines. The paternal contribution to adaptive processes in the offspring might be crucial, but has been widely neglected in comparison to the maternal one. To address the paternal impact on the offspring's adaptability to changes in diet composition, we investigated if low protein diet (LPD) in F0 males caused epigenetic alterations in their subsequently sired sons. We therefore fed F0 male Wild guinea pigs with a diet lowered in protein content (LPD) and investigated DNA methylation in sons sired before and after their father's LPD treatment in both, liver and testis tissues. Our results point to a 'heritable epigenetic response' of the sons to the fathers' dietary change. Because we detected methylation changes also in the testis tissue, they are likely to be transmitted to the F2 generation. Gene-network analyses of differentially methylated genes in liver identified main metabolic pathways indicating a metabolic reprogramming ('metabolic shift'). Epigenetic mechanisms, allowing an immediate and inherited adaptation may thus be important for the survival of species in the context of a persistently changing environment, such as climate change.},
  language  = {en}
}
@article{WeyrichGuerreroAltamiranoYasaretal.2022,
  author    = {Weyrich, Alexandra and Guerrero-Altamirano, Tania P. and Yasar, Selma and Czirjak, G{\´a}bor-{\´A}rp{\´a}d and Wachter, Bettina and Fickel, J{\"o}rns},
  title     = {First Steps towards the development of epigenetic biomarkers in female cheetahs (Acinonyx jubatus)},
  series = {Life : open access journal},
  volume    = {12},
  journal   = {Life : open access journal},
  number    = {6},
  publisher = {MDPI},
  address   = {Basel},
  issn      = {2075-1729},
  doi       = {10.3390/life12060920},
  pages     = {16},
  year      = {2022},
  abstract  = {Free-ranging cheetahs (Acinonyx jubatus) are generally healthy, whereas cheetahs under human care, such as those in zoological gardens, suffer from ill-defined infectious and degenerative pathologies. These differences are only partially explained by husbandry management programs because both groups share low genetic diversity. However, mounting evidence suggests that physiological differences between populations in different environments can be tracked down to differences in epigenetic signatures. Here, we identified differentially methylated regions (DMRs) between free-ranging cheetahs and conspecifics in zoological gardens and prospect putative links to pathways relevant to immunity, energy balance and homeostasis. Comparing epigenomic DNA methylation profiles obtained from peripheral blood mononuclear cells (PBMCs) from eight free-ranging female cheetahs from Namibia and seven female cheetahs living in zoological gardens within Europe, we identified DMRs of which 22 were hypermethylated and 23 hypomethylated. Hypermethylated regions in cheetahs under human care were located in the promoter region of a gene involved in host-pathogen interactions (KLC1) and in an intron of a transcription factor relevant for the development of pancreatic beta-cells, liver, and kidney (GLIS3). The most canonical mechanism of DNA methylation in promoter regions is assumed to repress gene transcription. Taken together, this could indicate that hypermethylation at the promoter region of KLC1 is involved in the reduced immunity in cheetahs under human care. This approach can be generalized to characterize DNA methylation profiles in larger cheetah populations under human care with a more granular longitudinal data collection, which, in the future, could be used to monitor the early onset of pathologies, and ultimately translate into the development of biomarkers with prophylactic and/or therapeutic potential.},
  language  = {en}
}